Down Syndrome (DS), trisomy of chromosome 21 (HSA21), is the most prevalent form of mental retardation caused by genetic abnormalities in humans (Epstein et al., 1990). Extra copies of all or part of HSA21 affect a number of organs, in particular the central nervous system. In addition to intellectual dysfunction, people with DS may suffer from congenital cardiac disease, immune and endocrine problems, genitourinary defects, gastrointestinal abnormalities, and orofacial malformations (Greenwood and Nadas, 1976; Korenberg et al., 1994; Cleves et al., 2007). An important characteristic of DS is the development of the neuropathological markers of Alzheimer's disease (AD) by age 40 and frequently, in later life, of cognitive decline (Burger and Vogel, 1973; Casanova et al., 1985; Mufson et al., 2002). Ts65Dn mice are the most commonly used mouse model of DS. They are segmentally trisomic for mouse chromosome 16 (MMU16), which is generated by Robertsonian segmental translocation of MMU16 to the MMU17 centromere (Davisson et al., 1990). The chromosomal segment contains an extra copy of more than 104 genes with homologues on HSA21 (Reeves et al., 1995; Baxter et al., 2000; Kahlem et al., 2004). Ts65Dn mice have shorter life expectancies and show morphological, neurological, and structural abnormalities that parallel those in people with DS (Dierssen et al., 1996; Holtzman et al., 1996; Dierssen et al., 1997; Granholm et al., 2000; Belichenko et al., 2004; Lumbreras et al., 2006; Salehi et al., 2006; Salehi et al., 2007). They show changes in the structure and function of neuronal circuits, including deficits in hippocampal synaptic plasticity, as demonstrated in both cellular signaling and electrophysiological studies (Dierssen et al., 1996; Dierssen et al., 1997; Siarey et al., 1997; Siarey et al., 1999; Kleschevnikov et al., 2004; Siarey et al., 2005; Siarey et al., 2006). Ts65Dn mice also share behavioral abnormalities similar to those seen in DS, along with increased locomotor activity (Davisson et al., 1993; Escorihuela et al., 1995; Reeves et al., 1995; Coussons-Read and Crnic, 1996; Stewart et al., 2007). Male trisomic mice show increased repetitive and stereotypical movement in the home cage. Ts65Dn mice have also shown impaired learning and memory, especially in hippocampus-dependent tasks, including the water maze spatial learning task (Escorihuela et al., 1995; Reeves et al., 1995; Demas et al., 1996; Holtzman et al., 1996), context discrimination learning (Hyde et al., 2001a), dry and water radial arm maze tests (Demas et al., 1996, 1998; Bimonte-Nelson et al., 2003; Hunter et al., 2004), and spontaneous alternation (Belichenko et al., 2007; Chang and Gold, 2008). However, in some learning and memory tests, such as passive avoidance, no significant difference was reported (Coussons-Read and Crnic, 1996; Holtzman et al., 1996; Rueda et al., 2008).
Despite the fact that many studies have been conducted and many changes have been noted in this model, No therapeutic treatments or approaches have been developed for this disorder.